ARISE I Consensus Review on the Management of Intracranial Aneurysms.

BACKGROUND: Intracranial aneurysms (IAs) remain a challenging neurological diagnosis associated with significant morbidity and mortality. There is a plethora of microsurgical and endovascular techniques for the treatment of both ruptured and unruptured aneurysms. There is no definitive consensus as to the best treatment option for this cerebrovascular pathology. The Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts discussed best practices and the most promising approaches to improve the management of brain aneurysms. METHODS: A group of experts from academia, industry, and federal regulators convened to discuss updated clinical trials, scientific research on preclinical system models, management options, screening and monitoring, and promising novel device technologies, aiming to improve the outcomes of patients with IA. RESULTS: Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts suggested the incorporation of artificial intelligence to capture sequential aneurysm growth, identify predictors of rupture, and predict the risk of rupture to guide treatment options. The consensus strongly recommended nationwide systemic data collection of unruptured IA radiographic images for the analysis and development of machine learning algorithms for rupture risk. The consensus supported centers of excellence for preclinical multicenter trials in areas such as genetics, cellular composition, and radiogenomics. Optical coherence tomography and magnetic resonance imaging contrast-enhanced 3T vessel wall imaging are promising technologies; however, more data are needed to define their role in IA management. Ruptured aneurysms are best managed at large volume centers, which should include comprehensive patient management with expertise in microsurgery, endovascular surgery, neurology, and neurocritical care. CONCLUSIONS: Clinical and preclinical studies and scientific research on IA should engage high-volume centers and be conducted in multicenter collaborative efforts. The future of IA diagnosis and monitoring could be enhanced by the incorporation of artificial intelligence and national radiographic and biologic registries. A collaborative effort between academic centers, government regulators, and the device industry is paramount for the adequate management of IA and the advancement of the field.

Predictors of acute post-thrombectomy intracranial hemorrhage expansion in anterior circulation infarcts.

BACKGROUND: Post-mechanical thrombectomy (MT) intracranial hemorrhage (ICH) is a major source of morbidity in treated acute ischemic stroke patients with large vessel occlusion. ICH expansion may further contribute to morbidity. We sought to identify factors associated with ICH expansion on imaging evaluation post-MT. METHODS: We performed a retrospective cohort study of patients undergoing MT at a single comprehensive stroke center. Per protocol, patients underwent dual-energy head CT (DEHCT) post-MT followed by a 24-h interval non-contrast enhanced MRI. ICH expansion was defined as any increase in blood volume between the two studies if identified on the DEHCT. Univariate and multivariable analyses were performed to identify risk factors for ICH expansion. RESULTS: ICH was identified on DEHCT in 13% of patients (n = 35/262), with 20% (7/35) demonstrating expansion on interval MRI. The average increase in blood volume was 11.4 ml (SD 6.9). Univariate analysis identified anticoagulant usage (57% vs 14%, p = 0.03), petechial hemorrhage inside the infarct margins or intraparenchymal hematoma on DEHCT (ECASS-II HI2/PH1/PH2) (71% vs 14%, p < 0.01), basal ganglia hemorrhage (71% vs 21%, p = 0.02), and basal ganglia infarction (86% vs 32%, p = 0.03) as factors associated with ICH expansion. Multivariate regression demonstrated that anticoagulant usage (OR 20.3, 95% C.I. 2.43-446, p < 0.05) and ECASS II scores of HI2/PH1/PH2 (OR 11.7, 95% C.I. 1.24-264, p < 0.05) were significantly predictive of ICH expansion. CONCLUSION: Expansion of post-MT ICH on 24-h interval MRI relative to immediate post-thrombectomy DEHCT is significantly associated with baseline anticoagulant usage and petechial hemorrhage inside the infarct margins or presence of intraparenchymal hematoma (ECASS-II HI2/PH1/PH2).

Analysis of frictional forces in experimental models of stent retriever mechanical thrombectomy.

Acute ischemic stroke (AIS) and mechanical thrombectomy (MT) are commonly studied in vitro using cerebral artery models made of nonbiological materials. However, these models often report higher recanalization rates than those observed clinically, suggesting a discrepancy between experimental models and clinical settings. We believe this may be partly due to the frictional interactions between blood clots, stent retrievers (SRs), and the vessel walls. Experiments were performed to measure the coefficients of static and kinetic friction between blood clots, common nonbiological model materials, and bovine carotid arteries (CAs). Additional friction testing was performed with nitinol SRs. Coefficients of static friction between blood clots and nonbiological materials were found to range from 0.1 to 0.2, increasing with decreasing clot hematocrit, but were significantly higher between blood clots and CAs (1.49, 0.57, and 0.46 for 0, 20, and 40% hematocrit clots, respectively). For 0% and 40% hematocrit clots, the coefficients of kinetic friction with nonbiological materials were less than 0.1, while significantly higher with CAs (0.26 and 0.23 for 0% and 40% hematocrit clots, respectively). However, no significant differences in the coefficients of kinetic friction were found between the different hematocrit clots. Testing with the nitinol SR showed no significant differences in the coefficients of kinetic friction for CAs (0.73) and silicone (0.78), suggesting that silicone could be a suitable model material for evaluating SR-vessel interactions in vitro. Overall, it is evident that discrepancies exist in the frictional forces between materials commonly used in experimental models of AIS and MT and those seen in vivo. The individual contributions of clot-artery, SR-artery, and clot-SR interactions during blood clot removal merit further investigation.

Experimental evaluation of the plunger technique: A method of cyclic manual aspiration thrombectomy for treatment of acute ischemic stroke.

BACKGROUND: Mechanical thrombectomy via direct aspiration is a rapid treatment for acute ischemic stroke. This method often results in the partial ingestion of the clot or "corking" of the catheter tip. Cyclic aspiration may take advantage of the mechanical properties of the clot, resulting in greater clot ingestion and overall procedure success. METHODS: An in vitro analysis was performed comparing static and cyclic (plunger technique) aspiration. Embolus analogs were used to create occlusions in a mock circulatory flow loop, and one aspiration attempt (first pass effect) using either a static or plunger technique was performed. The percent ingestion of each embolus analog was recorded for each trial. RESULTS: Static aspiration for 0% and 50% hematocrit embolus analogs resulted in ingestions of 12.8 ± 4.6% and 15.1 ± 10.0%, respectively, while plunger technique (cyclic) aspiration resulted in 15.8 ± 7.3% and 34.4 ± 19.5% ingestion. Complete ingestion was observed only with 50% hematocrit analogs, occurring in 30% of plunger and 10% of static cases. Statistical differences were determined between the two aspiration techniques for the 50% hematocrit samples, with the plunger technique yielding significantly more ingestion. In addition, the plunger technique was shown to maintain a negative vacuum pressure throughout the duration of cyclic plunging. CONCLUSIONS: The plunger technique for manual cyclic aspiration resulted in higher rates of complete ingestion and greater average % ingestions when compared to static aspiration. Increased clot ingestion can result in a higher rate of complete reperfusion during the first aspiration attempt, maximizing the number of patients with good clinical outcomes.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Primary results from the CLEAR study of a novel stent retriever with drop zone technology.

BACKGROUND: Challenges to revascularization of large vessel occlusions (LVOs) persist. Current stent retrievers have limited effectiveness for removing organized thrombi. The NeVa device is a novel stent retriever designed to capture organized thrombi within the scaffold during retrieval. OBJECTIVE: To evaluate the safety and effectiveness of revascularization of acute LVOs with the NeVa device. METHODS: Prospective, international, multicenter, single-arm, Investigational Device Exemption study to evaluate the performance of the NeVa device in recanalizing LVOs including internal carotid artery, M1/M2 middle cerebral artery, and vertebrobasilar arteries, within 8 hours of onset. Primary endpoint was rate of expanded Treatment in Cerebral Ischemia (eTICI) score 2b-3 within 3 NeVa passes, tested for non-inferiority against a performance goal of 72% with a -10% margin. Additional endpoints included first pass success and 90-day modified Rankin Scale (mRS) score 0-2. Primary composite safety endpoint was 90-day mortality and/or 24-hour symptomatic intracranial hemorrhage (sICH). RESULTS: From April 2021 to April 2022, 139 subjects were enrolled at 25 centers. Median National Institutes of Health Stroke Scale (NIHSS) score was 16 (IQR 12-20). In the primary analysis population (n=107), eTICI 2b-3 within 3 NeVa passes occurred in 90.7% (97/107; non-inferiority P<0.0001; post hoc superiority P<0.0001). First pass eTICI 2b-3 was observed in 73.8% (79/107), with first pass eTICI 2b67-3 in 69.2% (74/107) and eTICI 2c-3 in 48.6% (52/107). Median number of passes was 1 (IQR 1-2). Final eTICI 2b-3 rate was 99.1% (106/107); final eTICI 2b67-3 rate was 91.6% (98/107); final eTICI 2c-3 rate was 72.9% (78/107). Good outcome (90-day mRS score 0-2) was seen in 65.1% (69/106). Mortality was 9.4% (13/138) with sICH in 5.0% (7/139). CONCLUSIONS: The NeVa device is highly effective and safe for revascularization of LVO strokes and demonstrates superior first pass success compared with a predicate performance goal. TRIAL REGISTRATION NUMBER: NCT04514562.

The 'plunger' technique for direct aspiration thrombectomy.

Direct aspiration thrombectomy is often employed for endovascular treatment of acute ischemic stroke because it rapidly achieves recanalization. Ideally, the clot is completely or nearly completely ingested into the aspiration catheter. Static aspiration is typically used, either with an electrical pump1 or with a handheld syringe, which applies a fixed vacuum. However, cyclic or oscillating aspiration may lead to additional deformation of the clot, which allows for additional ingestion into the catheter.2-4 This video describes the use of the 'plunger' technique, wherein a 60 mL locking syringe is used to apply on/off vacuum force to the occlusive clot. This technique provides a simple, manual approach to cyclic aspiration for stroke thrombectomy (video 1).neurintsurg;jnis-2023-021067v2/V1F1V1Video 1.

Blood Pressure Management After Endovascular Therapy for Acute Ischemic Stroke: The BEST-II Randomized Clinical Trial.

Importance: The effects of moderate systolic blood pressure (SBP) lowering after successful recanalization with endovascular therapy for acute ischemic stroke are uncertain. Objective: To determine the futility of lower SBP targets after endovascular therapy (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg). Design, Setting, and Participants: Randomized, open-label, blinded end point, phase 2, futility clinical trial that enrolled 120 patients with acute ischemic stroke who had undergone successful endovascular therapy at 3 US comprehensive stroke centers from January 2020 to March 2022 (final follow-up, June 2022). Intervention: After undergoing endovascular therapy, participants were randomized to 1 of 3 SBP targets: 40 to less than 140 mm Hg, 40 to less than 160 mm Hg, and 40 to 180 mm Hg or less (guideline recommended) group, initiated within 60 minutes of recanalization and maintained for 24 hours. Main Outcomes and Measures: Prespecified multiple primary outcomes for the primary futility analysis were follow-up infarct volume measured at 36 (±12) hours and utility-weighted modified Rankin Scale (mRS) score (range, 0 [worst] to 1 [best]) at 90 (±14) days. Linear regression models were used to test the harm-futility boundaries of a 10-mL increase (slope of 0.5) in the follow-up infarct volume or a 0.10 decrease (slope of -0.005) in the utility-weighted mRS score with each 20-mm Hg SBP target reduction after endovascular therapy (1-sided α = .05). Additional prespecified futility criterion was a less than 25% predicted probability of success for a future 2-group, superiority trial comparing SBP targets of the low- and mid-thresholds with the high-threshold (maximum sample size, 1500 with respect to the utility-weighted mRS score outcome). Results: Among 120 patients randomized (mean [SD] age, 69.6 [14.5] years; 69 females [58%]), 113 (94.2%) completed the trial. The mean follow-up infarct volume was 32.4 mL (95% CI, 18.0 to 46.7 mL) for the less than 140-mm Hg group, 50.7 mL (95% CI, 33.7 to 67.7 mL), for the less than 160-mm Hg group, and 46.4 mL (95% CI, 24.5 to 68.2 mL) for the 180-mm Hg or less group. The mean utility-weighted mRS score was 0.51 (95% CI, 0.38 to 0.63) for the less than 140-mm Hg group, 0.47 (95% CI, 0.35 to 0.60) for the less than 160-mm Hg group, and 0.58 (95% CI, 0.46 to 0.71) for the high-target group. The slope of the follow-up infarct volume for each mm Hg decrease in the SBP target, adjusted for the baseline Alberta Stroke Program Early CT score, was -0.29 (95% CI, -0.81 to ∞; futility P = .99). The slope of the utility-weighted mRS score for each mm Hg decrease in the SBP target after endovascular therapy, adjusted for baseline utility-weighted mRS score, was -0.0019 (95% CI, -∞ to 0.0017; futility P = .93). Comparing the high-target SBP group with the lower-target groups, the predicted probability of success for a future trial was 25% for the less than 140-mm Hg group and 14% for the 160-mm Hg group. Conclusions and Relevance: Among patients with acute ischemic stroke, lower SBP targets less than either 140 mm Hg or 160 mm Hg after successful endovascular therapy did not meet prespecified criteria for futility compared with an SBP target of 180 mm Hg or less. However, the findings suggested a low probability of benefit from lower SBP targets after endovascular therapy if tested in a future larger trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04116112.

Low Levels of Low-Density Lipoprotein Cholesterol Increase the Risk of Post-Thrombectomy Delayed Parenchymal Hematoma.

PURPOSE: Low levels of low-density lipoprotein cholesterol (LDL-C) have been suggested to increase the risk of hemorrhagic transformation (HT) following acute ischemic stroke. However, the literature on the relationship between LDL-C levels and post-thrombectomy HT is sparse. The aim of our study is to investigate the association between LDL-C and delayed parenchymal hematoma (PH) that was not seen on immediate post-thrombectomy dual-energy computed tomography (DECT). MATERIALS AND METHODS: A retrospective analysis was conducted on all patients with anterior circulation large vessel occlusion who underwent thrombectomy at a comprehensive stroke center from 2018-2021. Per institutional protocol, all patients received DECT immediately post-thrombectomy and magnetic resonance imaging or CT at 24 hours. The presence of immediate hemorrhage was assessed by DECT, while delayed PH was assessed by 24-hour imaging. Multivariable analysis was performed to identify predictors of delayed PH. Patients with hemorrhage on immediate post-thrombectomy DECT were excluded to select only those with delayed PH. RESULTS: Of 159 patients without hemorrhage on immediate post-thrombectomy DECT, 18 (11%) developed delayed PH on 24-hour imaging. In multivariable analysis, LDL-C (odds ratio [OR], 0.76; P=0.038; 95% confidence interval [CI], 0.59-0.99; per 10 mg/dL increase) independently predicted delayed PH. High-density lipoprotein cholesterol, triglyceride, and statin use were not associated. After adjusting for potential confounders, LDL-C ≤50 mg/dL was associated with an increased risk of delayed PH (OR, 5.38; P=0.004; 95% CI, 1.70-17.04), while LDL-C >100 mg/dL was protective (OR, 0.26; P=0.041; 95% CI, 0.07-0.96). CONCLUSION: LDL-C ≤50 mg/dL independently predicted delayed PH following thrombectomy and LDL-C >100 mg/dL was protective, irrespective of statin. Thus, patients with low LDL-C levels may warrant vigilant monitoring and necessary interventions, such as blood pressure control or anticoagulation management, following thrombectomy even in the absence of hemorrhage on immediate post-thrombectomy DECT.

Emerging Subspecialties in Neurology: Interventional Neurology: A Starter Guide for Neurology Residents.

Interventional neurology is a subspecialty at the cross-section of neurology, neurosurgery, and neuroradiology that uses image-guided endovascular catheter techniques to diagnose and treat neurovascular disorders. Although interventional neurology techniques have existed for decades, recent landmark trials in stroke thrombectomy have catalyzed dramatic changes to the interventional neurology field, and there is rising neurology interest and representation. Unlike other neurology subspecialties, however, interventional neurology training and fellowship applications are not standardized. Thus, it can be difficult for neurology trainees to navigate this rapidly changing and multidisciplinary field. This article seeks to provide neurology residents and residency program directors with a brief overview of the modern interventional neurology field, the current fellowship application process, and tips on how neurologists can best prepare for a career in interventional neurology. To this end, we conducted a nationwide survey of interventional neurology fellowship program directors regarding training neurologists. We distill survey responses into concrete, actionable items for neurology trainees.

The clinical utility of dual-energy CT in post-thrombectomy care: Part 2, the predictive value of contrast density and volume for delayed hemorrhagic transformation.

OBJECTIVES: Dual-energy CT allows differentiation between blood and iodinated contrast. This study aims to determine the predictive value of contrast density and volume on post-thrombectomy dual-energy CT for delayed hemorrhagic transformation and its impact on 90-day outcomes. MATERIALS AND METHODS: A retrospective analysis was performed on patients who underwent thrombectomy for anterior circulation large-vessel occlusion at a comprehensive stroke center from 2018-2021. Per institutional protocol, all patients underwent dual-energy CT immediately post-thrombectomy and MRI or CT 24 hours afterward. The presence of hemorrhage and contrast staining was evaluated by dual-energy CT. Delayed hemorrhagic transformation was determined by 24-hour imaging and classified into petechial hemorrhage or parenchymal hematoma using ECASS III criteria. Univariable and multivariable analyses were performed to determine predictors and outcomes of delayed hemorrhagic transformation. RESULTS: Of 97 patients with contrast staining and without hemorrhage on dual-energy CT, 30 and 18 patients developed delayed petechial hemorrhage and delayed parenchymal hematoma, respectively. On multivariable analysis, delayed petechial hemorrhage was predicted by anticoagulant use (OR,3.53;p=0.021;95%CI,1.19-10.48) and maximum contrast density (OR,1.21;p=0.004;95%CI,1.06-1.37;per 10 HU increase), while delayed parenchymal hematoma was predicted by contrast volume (OR,1.37;p=0.023;95%CI,1.04-1.82;per 10 mL increase) and low-density lipoprotein (OR,0.97;p=0.043;95%CI,0.94-1.00;per 1 mg/dL increase). After adjusting for potential confounders, delayed parenchymal hematoma was associated with worse functional outcomes (OR,0.07;p=0.013;95%CI,0.01-0.58) and mortality (OR,7.83;p=0.008;95%CI,1.66-37.07), while delayed petechial hemorrhage was associated with neither. CONCLUSION: Contrast volume predicted delayed parenchymal hematoma, which was associated with worse functional outcomes and mortality. Contrast volume can serve as a useful predictor of delayed parenchymal hematoma following thrombectomy and may have implications for patient management.

The clinical utility of dual-energy CT in post-thrombectomy care: Part 1, predictors and outcomes of subarachnoid and intraparenchymal hemorrhage.

OBJECTIVES: Dual-energy CT allows differentiation between blood and iodinated contrast. We aimed to determine predictors of subarachnoid and intraparenchymal hemorrhage on dual-energy CT performed immediately post-thrombectomy and the impact of these hemorrhages on 90-day outcomes. MATERIALS AND METHODS: A retrospective analysis was performed on patients who underwent thrombectomy for anterior circulation large-vessel occlusion and subsequent dual-energy CT at a comprehensive stroke center from 2018-2021. The presence of contrast, subarachnoid hemorrhage, or intraparenchymal hemorrhage immediately post-thrombectomy was assessed by dual-energy CT. Univariable and multivariable analyses were performed to identify predictors of post-thrombectomy hemorrhages and 90-day outcomes. Patients with unknown 90-day mRS were excluded. RESULTS: Of 196 patients, subarachnoid hemorrhage was seen in 17, and intraparenchymal hemorrhage in 23 on dual-energy CT performed immediately post-thrombectomy. On multivariable analysis, subarachnoid hemorrhage was predicted by stent retriever use in the M2 segment of MCA (OR,4.64;p=0.017;95%CI,1.49-14.35) and the number of thrombectomy passes (OR,1.79;p=0.019;95%CI,1.09-2.94;per an additional pass), while intraparenchymal hemorrhage was predicted by preprocedural non-contrast CT-based ASPECTS (OR,8.66;p=0.049;95%CI,0.92-81.55;per 1 score decrease) and preprocedural systolic blood pressure (OR,5.10;p=0.037;95%CI,1.04-24.93;per 10 mmHg increase). After adjusting for potential confounders, intraparenchymal hemorrhage was associated with worse functional outcomes (OR,0.25;p=0.021;95%CI,0.07-0.82) and mortality (OR,4.30;p=0.023,95%CI,1.20-15.36), while subarachnoid hemorrhage was associated with neither. CONCLUSIONS: Intraparenchymal hemorrhage immediately post-thrombectomy was associated with worse functional outcomes and mortality and can be predicted by low ASPECTS and elevated preprocedural systolic blood pressure. Future studies focusing on management strategies for patients presenting with low ASPECTS or elevated blood pressure to prevent post-thrombectomy intraparenchymal hemorrhage are warranted.

Angiographic analysis of ophthalmic artery flow direction in children undergoing chemosurgery for retinoblastoma compared to age-matched controls.

PURPOSE: Catheter-based intra-arterial chemotherapy (IAC) has revolutionized the treatment of retinoblastoma (RB). Variability in ophthalmic artery (OA) flow, either retrograde from external carotid artery branches, or anterograde from the internal carotid artery, necessitates multiple IAC techniques. We evaluated the direction of OA flow and identify OA flow reversal events over the course of IAC treatment as well in comparison to OA flow direction in non-RB children. MATERIALS AND METHODS: We performed a retrospective analysis of OA flow direction in all RB patients treated with IAC, along with an age-matched control group who underwent cerebral angiography at our center from 2014 to 2020. RESULTS: IAC was administered to a total of 18 eyes (15 patients). Initial anterograde OA flow was demonstrated in 66% (n = 12) of eyes. Five OA reversal events were identified (3/5 anterograde-to-retrograde). All five events were in patients receiving multiagent chemotherapy. No correlation was found between OA flow reversal events and the initial IAC technique. A control group of 88 angiograms representing 82 eyes (41 patients) was utilized. The anterograde flow was observed in 76 eyes (86.4%). Our control group included 19 patients with sequential angiograms. One OA flow reversal event was identified. CONCLUSION: OA flow direction is dynamic in IAC patients. Anterograde and retrograde OA directional switches do occur and may necessitate delivery technique variation. In our analysis, all OA flow reversal events were associated with multiagent chemotherapy regimens. Both anterograde and retrograde OA flow patterns were observed in our control cohort, suggesting bidirectional flow can occur in non-RB children.

Flat-panel dual-energy head computed tomography in the angiography suite after thrombectomy for acute stroke: A clinical feasibility study.

BACKGROUND: Management of large vessel occlusion (LVO) patients after thrombectomy is affected by the presence of intracranial hemorrhage (ICH) on post-procedure imaging. Differentiating contrast staining from hemorrhage on post-procedural imaging has been facilitated by dual-energy computed tomography (DECT), traditionally performed in dedicated computed tomography (CT) scanners with subsequent delays in treatment. We employed a novel method of DECT using the Siemens cone beam CT (DE-CBCT) in the angiography suite to evaluate for post-procedure ICH and contrast extravasation. METHODS: After endovascular treatment for LVO was performed and before the patient was removed from the operating table, DE-CBCT was performed using the Siemens Q-biplane system, with two separate 20-second CBCT scans at two energy levels: 70 keV (standard) and 125 keV with tin filtration (nonstandard). Post-procedurally, patients also underwent a standard DECT using Siemens SOMATOM Force CT scanner. Two independent reviewers blindly evaluated the DE-CBCT and DECT for hemorrhage and contrast extravasation. RESULTS: We successfully performed intra-procedural DE-CBCT in 10 subjects with no technical failure. The images were high-quality and subjectively useful to differentiate contrast from hemorrhage. The one hemorrhage seen on standard DECT was very small and clinically silent. The interrater reliability was 100% for both contrast and hemorrhage detection. CONCLUSION: We demonstrate that intra-procedural DE-CBCT after thrombectomy is feasible and provides clinically meaningful images. There was close agreement between findings on DE-CBCT and standard DECT. Our findings suggest that DE-CBCT could be used in the future to improve stroke thrombectomy patient workflow and to more efficiently guide the postoperative management of these patients.

Oral health and functional outcomes following mechanical thrombectomy for ischemic stroke.

BACKGROUND: An association between poor dentition and the risk of ischemic stroke has previously been reported in the literature. In this study we assessed oral hygiene (OH), including tooth loss and the presence of dental disease, to determine if an association exists with functional outcomes following mechanical thrombectomy (MT) for large-vessel ischemic stroke. METHODS: A retrospective review was conducted of consecutive adult patients at a single comprehensive stroke center who underwent MT from 2012 to 2018. Inclusion criteria included availability of CT imaging to radiographically assess OH. A multivariate analysis was performed, with the primary outcome being 90-day post-thrombectomy modified Rankin Scale (mRS) score >2. RESULTS: A total of 276 patients met the inclusion criteria. The average number of missing teeth was significantly higher in patients with a poor functional outcome (mean (SD) 10 (11) vs 4 (6), p<0.001). The presence of dental disease was associated with poor functional outcome, including cavities (21 (27%) vs 13 (8%), p<0.001), periapical infection (18 (23%) vs 11 (6.7%), p<0.001), and bone loss (27 (35%) vs 11 (6.7%), p<0.001). Unadjusted, missing teeth was a univariate predictor of poor outcome (OR 1.09 (95% CI 1.06 to 1.13), p<0.001). After adjustment for recanalization scores and use of tissue plasminogen activator (tPA), missing teeth remained a predictor of poor outcome (OR 1.07 (95% CI 1.03 to 1.11), p<0.001). CONCLUSION: Missing teeth and the presence of dental disease are inversely correlated with functional independence following MT, independent of thrombectomy success or tPA status.

A Phase III, prospective, double-blind, randomized, placebo-controlled trial of thrombolysis in imaging-eligible, late-window patients to assess the efficacy and safety of tenecteplase (TIMELESS): Rationale and design.

RATIONALE: While thrombolysis is standard of care for patients with acute ischemic stroke (AIS) within 4.5 h of symptom onset, the benefit of tenecteplase beyond this time window is less certain. AIM: The TIMELESS trial (NCT03785678) aims to determine if treatment with tenecteplase increases the proportion of good clinical outcomes among patients with stroke due to a large vessel occlusion who present beyond 4.5 h after symptom onset. SAMPLE SIZE ESTIMATES: A total of 456 patients will provide ⩾90% power to detect differences in the distribution of modified Rankin Scale scores at Day 90 at the two-sided 0.049 significance level. METHODS AND DESIGN: TIMELESS is a Phase III, double-blind, randomized, placebo-controlled trial of tenecteplase with or without endovascular thrombectomy in patients with AIS and evidence of salvageable tissue via imaging who present within the 4.5- to 24-h time window with an internal carotid artery (ICA) or middle cerebral artery (MCA) (M1/M2) occlusion. STUDY OUTCOMES: The primary efficacy objective of tenecteplase compared with placebo will be evaluated with ordinal modified Rankin Scale scores at Day 90. Safety will be evaluated via incidence of symptomatic intracranial hemorrhage, incidence and severity of adverse events, and mortality rate. DISCUSSION: Results from TIMELESS will contribute to understanding of the safety and efficacy of tenecteplase administered 4.5-24 h following symptom onset for patients with an ICA or MCA occlusion.

IV Thrombolysis Initiated Before Transfer for Endovascular Stroke Thrombectomy: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: The role of IV thrombolysis (IVT) in patients with large vessel occlusions (LVOs) administered before transfer from a primary stroke center (PSC) to a comprehensive stroke center (CSC) is questioned. METHODS: We included observational studies of patients with an LVO receiving IVT at a PSC before their endovascular thrombectomy (EVT) transfer compared with those receiving EVT alone. Efficacy outcomes included excellent or good functional outcomes (modified Rankin Scale [mRS] scores of 0-1 or 0-2, respectively) and reduced disability (mRS shift analysis) at 3 months. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 48 hours and 3-month all-cause mortality. Associations are reported with crude odds ratios (ORs) and adjusted ORs (aORs). RESULTS: We identified 6 studies, including 1,723 participants (mean age: 71 years, 51% women; 53% treated with IVT at a PSC). The mean onset-to-groin puncture time did not differ between the 2 groups (mean difference: -20 minutes, 95% CI -115.89 to 76.04). Patients receiving IVT before transfer had higher odds of 3-month reduced disability (common OR = 1.98, 95% CI 1.17-3.35), excellent (OR = 1.70, 95% CI 1.28-2.26), and good (OR = 1.62.95% CI 1.15-2.29) functional outcomes, with no increased sICH (OR = 0.87, 95% CI 0.54-1.39) or mortality (OR = 0.55, 95% CI 0.37-0.83) risks. In the adjusted analyses, patients receiving IVT at a PSC had higher odds of excellent functional outcome (aOR = 1.32, 95% CI 1.00-1.74) and a lower probability for mortality (aOR = 0.50, 95% CI 0.27-0.93). DISCUSSION: Patients with LVO receiving IVT at a PSC before an EVT transfer have a higher likelihood of excellent functional recovery and lower odds of mortality, with no increase in sICH and onset-to-groin puncture times, compared with those transferred for EVT without previously receiving IVT.

Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial.

BACKGROUND: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03192332.